Schistosomiasis is the second major parasitic disease in the world after malaria. It affects 201.5 million cases in Africa alone. The aim of this research was to explore alternative vaccination strategies against experimental schistosomiasis mansoni. We assessed the effect of cercarial transformation fluid (CTF) singly and in combination with crude cercarial antigen (CCA) using alum as an adjuvant. The combined antigens gave the best results, as evidenced by a significant reduction in the worm load (62.07%), tissue egg count (78.16%, 86.46%) in liver and intestine respectively, and hepatic granuloma size (29.96%). Scanning electron microscopy revealed changes in the tegument, in the form of roughness and appearance of vesicles and furrows between the tegumental tubercles. Also, resorption of the ventral sucker and dimples replacing its spines were observed. The female tegument was irregular and its posterior end showed loss of spines and sensory bulbs. Moreover, there was a significant decrease in liver enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)) compared to infected control mice. A significant elevation in CD4+T-lymphocytes, denoting amelioration of the immune status, in mice that received combined antigens was also observed. It can be concluded that combined antigens demonstrate potential as a vaccine against Schistosoma mansoni.